Synthetic HIV gag genes

Abstract

Synthetic DNA molecules encoding HIV gag and modifications of HIV gag are provided. The codons of the synthetic molecules are codons preferred by the projected host cell. The synthetic molecules may be used as a polynucleotide vaccine which provides effective immunoprophylaxis against HIV infection through stimulation of neutralizing antibody and cell-mediated immunity.

What is claimed is:  
     
         1 . A synthetic polynucleotide comprising a DNA sequence encoding a nonmammalian protein or fragment thereof, the DNA sequence comprising codons optimized for expression in a mammalian host.  
     
     
         2 . The polynucleotide of  claim 1  wherein the protein is selected from HIV proteins, HSV proteins, HAV proteins, HBV proteins, HCV proteins, HPV proteins, HSV proteins, Plasmodium proteins, Mycobacterium proteins, Borrelia proteins and rotavirus proteins.  
     
     
         3 . The polynucleotide of  claim 2  wherein the protein is an HIV protein.  
     
     
         4 . The polynucleotide of  claim 3  having the following DNA sequence:  
       
         
           
                 
                 
                 
                 
               
                     
                 
                   1 
                   AGATCTACCA TGGGTGCTAG GGCTTCTGTG CTGTCTGGTG GTGAGCTGGA 
                   (SEQ ID NO:1) 
                     
                 
                     
                 
                   51 
                   CAAGTGGGAG AAGATCAGGC TGAGGCCTGG TGGCAAGAAG AAGTACAAGC 
                 
                     
                 
                   101 
                   TAAAGCACAT TGTGTGGGCC TCCAGGGAGC TGGAGAGGTT TGCTGTGAAC 
                 
                     
                 
                   151 
                   CCTGGCCTGC TGGAGACCTC TGAGGGGTGC AGGCAGATCC TGGGCCAGCT 
                 
                     
                 
                   201 
                   CCAGCCCTCC CTGCAAACAG GCTCTGAGGA GCTGAGGTCC CTGTACAACA 
                 
                     
                 
                   251 
                   CAGTGGCTAC CCTGTACTGT GTGCACCAGA AGATTGATGT GAAGGACACC 
                 
                     
                 
                   301 
                   AAGGAGGCCC TGGAGAAGAT TGAGGAGGAG CAGAACAAGT CCAAGAAGAA 
                 
                     
                 
                   351 
                   GGCCCAGCAG GCTGCTGCTG GCACAGGCAA CTCCAGCCAG GTGTCCCAGA 
                 
                     
                 
                   401 
                   ACTACCCCAT TGTGCAGAAC CTCCAGGGCC AGATGGTGCA CCAGGCCATC 
                 
                     
                 
                   451 
                   TCCCCCCGGA CCCTGAATGC CTGGGTGAAG GTGGTGGAGG AGAAGGCCTT 
                 
                     
                 
                   501 
                   CTCCCCTGAG GTGATCCCCA TGTTCTCTGC CCTGTCTGAG GGTGCCACCC 
                 
                     
                 
                   551 
                   CCCAGGACCT GAACACCATG CTGAACACAG TGGGGGGCCA TCAGGCTGCC 
                 
                     
                 
                   601 
                   ATGCAGATGC TGAAGGAGAC CATCAATGAG GAGGCTGCTG AGTGGGACAG 
                 
                     
                 
                   651 
                   GCTGCATCCT GTGCACGCTG GCCCCATTGC CCCCGGCCAG ATGAGGGAGC 
                 
                     
                 
                   701 
                   CCAGGGGCTC TGACATTGCT GGCACCACCT CCACCCTCCA GGAGCAGATT 
                 
                     
                 
                   751 
                   GGCTGGATGA CCAACAACCC CCCCATCCCT GTGGGGGAAA TCTACAAGAG 
                 
                     
                 
                   801 
                   GTGGATCATC CTGGGCCTGA ACAAGATTGT GAGGATGTAC TCCCCCACCT 
                 
                     
                 
                   851 
                   CCATCCTGGA CATCAGGCAG GGCCCCAAGG AGCCCTTCAG GGACTATGTG 
                 
                     
                 
                   901 
                   GACAGGTTCT ACAAGACCCT GAGGGCTGAG CAGGCCTCCC AGGAGGTGAA 
                 
                     
                 
                   951 
                   GAACTGGATG ACAGAGACCC TGCTGGTGCA GAATGCCAAC CCTGACTGCA 
                 
                     
                 
                   1001 
                   AGACCATCCT GAAGGCCCTG GGCCCTGCTG CCACCCTGGA GGAGATGATG 
                 
                     
                 
                   1051 
                   ACAGCCTGCC AGGGGGTGGG GGGCCCTGGT CACAAGGCCA GGGTGCTGGC 
                 
                     
                 
                   1101 
                   TGAGGCCATG TCCCAGGTGA CCAACTCCGC CACCATCATG ATGCAGAGGG 
                 
                     
                 
                   1151 
                   GCAACTTCAG GAACCAGAGG AAGACAGTGA AGTGCTTCAA CTGTGGCAAG 
                 
                     
                 
                   1201 
                   GTGGGCCACA TTGCCAAGAA CTGTAGGGCC CCCAGGAAGA AGGGCTGCTG 
                 
                     
                 
                   1251 
                   GAAGTGTGGC AAGGAGGGCC ACCAGATGAA GGACTGCAAT GAGAGGCAGG 
                 
                     
                 
                   1301 
                   CCAACTTCCT GGGCAAAATC TGGCCCTCCC ACAAGGGCAG GCCTGGCAAC 
                 
                     
                 
                   1351 
                   TTCCTCCAGT CCAGGCCTGA GCCCACAGCC CCTCCCGAGG AGTCCTTCAG 
                 
                     
                 
                   1401 
                   GTTTGGGGAG GAGAAGACCA CCCCCAGCCA GAAGCAGGAG CCCATTGACA 
                 
                     
                 
                   1451 
                   AGGAGCTGTA CCCCCTGGCC TCCCTGAGGT CCCTGTTTGG CAACGACCCC 
                 
                     
                 
                   1501 
                   TCCTCCCAGT AAAATAAAGC CCGGGCAGAT CT. 
                 
                     
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         5 . The polynucleotide of  claim 3  which induces anti-HIV neutralizing antibody, HIV specific T-cell immune responses, or protective immune responses upon introduction into vertebrate tissue, including human tissue in vivo, wherein the polynucleotide comprises a gene encoding an HIV gag, gag-protease, or env gene product.  
     
     
         6 . A method for inducing immune responses in a vertebrate which comprises introducing between 1 ng and 100 mg of the polynucleotide of  claim 1  into the tissue of the vertebrate.  
     
     
         7 . The method of  claim 6  which further comprises administration of attenuated pathogen, killed pathogen, subunit vaccines, protein vaccines and combinations thereof.  
     
     
         8 . An immunogenic composition for inducing immune responses against HIV infection which comprises the polynucleotide of  claim 3  and a pharmaceutically acceptable carrier, and optionally, an adjuvant.  
     
     
         9 . A method for inducing anti-HIV immune responses in a primate which comprises introducing the polynucleotide of  claim 3  into the tissue of said primate and concurrently administering a cytokine parenterally.  
     
     
         10 . A method of inducing an antigen presenting cell to stimulate cytotoxic and helper T-cell proliferation an effector functions including lymphokine secretion specific to HIV antigens which comprises exposing cells of a vertebrate in vivo to the polynucleotide of  claim 3 .  
     
     
         11 . A method of treating a patient in need of such treatment comprising administering to the patient the polynucleotide of  claim 3  in combination with an anti-HIV antiviral agent.  
     
     
         12 . A pharmaceutical composition comprising the polynucleotide of  claim 1.